Biology subjects

Harel, A.

Publications and source records attributed to Harel, A..

6 recordsLinked to original sources

bioRxiv2024

Plasticity of visual looming response reveals a dissociation of innate and learned components

Animals rely on innate and learned behaviour to respond to their environment, but how the brain balances hardwired responses with adaptive flexibility remains unclear. Here, we demonstrate that innate looming stimulus responses in mice can be attenuated via repeated unreinforced presentation. This attenuation is long-lasting and generalising, but is rapidly recovered when the stimulus is paired with an electric foot-shock. Fiber photometry recordings reveal attenuation of responses to visual looming stimuli in the SC and PAG, which do not recover following recovery of behavioural responses. Analysis of c-Fos expression uncovered a ventral CA1 (vCA1) ensemble that is active during both innate and learned looming fear responses. We report that this vCA1 engram is not necessary for innate defensive behaviour but is necessary for learned fear responses. These findings reveal a novel role of the hippocampus in adapting to looming stimuli, and provide a platform for understanding the interaction of memory and instinct.

neuroscience↗

bioRxiv2022

Locus c{oelig}ruleus noradrenergic neurons phase-lock to prefrontal cortical and hippocampal infra-slow rhythms which synchronize with behavioral events

The locus cruleus (LC) is the primary source of noradrenergic projections to the forebrain, and, in prefrontal cortex, is implicated in decision-making and executive function. LC neurons phase-lock to cortical infra-slow wave oscillations during sleep. Such infra-slow rhythms are rarely reported in awake states, despite their interest, since they correspond to the time scale of behavior. Thus, we investigated LC neuronal synchrony with infra-slow rhythms in awake rats performing an attentional set-shifting task. Local field potential (LFP) oscillation cycles in prefrontal cortex and hippocampus on the order of 0.4 Hz phase-locked to task events at crucial maze locations. Indeed, successive cycles of the infra-slow rhythms showed different wavelengths, as if they are periodic oscillations that can reset phase relative to salient events. Simultaneously recorded infra-slow rhythms in prefrontal cortex and hippocampus could show different cycle durations as well suggesting independent control. Most LC neurons (including optogenetically identified noradrenergic neurons) recorded here were phase-locked to these infra-slow rhythms, as were hippocampal and prefrontal units recorded on the LFP probes. The infra-slow oscillations also phase-modulated gamma amplitude, linking these rhythms at the time scale of behavior to those coordinating neuronal synchrony. This would provide a potential mechanism where noradrenaline, released by LC neurons in concert with the infra-slow rhythm, would facilitate synchronization or reset of these brain networks, underlying behavioral adaptation.

neuroscience↗

bioRxiv2021

Identification of a Major Locus for Flowering Pattern Sheds Light on Plant Architecture Diversification in Cultivated Peanut

Flowering pattern is a major taxonomic characteristic differentiating the two main subspecies of cultivated peanut (Arachis hypogaea L.). subsp. fastigiata possessing flowers on the mainstem (MSF) and a sequential flowering pattern, whereas subsp. hypogaea lacks flowers on the mainstem and exhibits an alternate flowering pattern. This character is considered the main contributor to plant architecture and the adaptability of each subgroup to specific growing conditions. Evidence indicates that flowering pattern differentiation occurred during the several thousand years of domestication and diversification in South America. However, the exact genetic mechanism that controls flowering pattern and the molecular changes that led to its historical diversification in peanut are unknown. We investigated the genetics of the flowering pattern in a recombinant inbred population of 259 lines (RILs), derivatives of an A. hypogaea and A. fastigiata cross. RILs segregated 1:1 in both the sequential/alternative and the MSF-plus/MSF-minus traits, indicating a single gene effect. Using the Axiom_Arachis2 SNP-array, MSF was mapped to a 1.7 Mbp segment on chromosome B02 of the cultivated A. hypogaea. Significant haplotype conservation was found for this locus in the USA peanut mini core collection, suggesting a possible selection upon hypogaea/fastigiata speciation. Furthermore, a candidate Terminal Flowering 1-like (AhTFL1) gene was identified within the MSF region, in which a 1492 bp deletion occurred in the fastigiata line that leads to a truncated protein product. Remapping MSF in the RIL population with the AhTFL1 deletion as a marker increased the LOD score from 53.3 to 158.8 with no recombination. The same deletion was also found to co-segregate with the phenotype in two EMS-mutagenized M2 families, suggesting a hotspot for large mutational deletion or gene conversion that may play a role in evolution. BLASTX analysis showed that the most similar homologous gene for TFL1-like in soybean is Det1, which previously was shown to control shoot determination. Sequence analysis of the TFL-1 in a series of domesticated lines showed that TFL1 was subjected to gain/loss events of the deletion, partly explaining the evolution of MSF in Arachis. Altogether, these results support the role of AhTFL-1 in peanut speciation during domestication and modern cultivation.

genetics↗

bioRxiv2020

The Nuclear Pore Complex consists of two independent scaffolds

Macromolecular transport between the nucleus and cytoplasm is mediated through Nuclear Pore Complexes (NPCs), which are built from multiple copies of roughly 34 distinct proteins, called nucleoporins1-3. Models of the NPC depict it as a composite of several sub-domains that have been named the outer rings, inner ring, cytoplasmic fibrils and nuclear basket. While the NPC has been extensively studied, the roles of individual nucleoporins within NPCs and their functional interactions remain poorly understood. Here, we applied a rapid degron system to systematically investigate how individual nucleoporins contribute toward NPC architecture. We find that acute depletion of outer ring components (NUP96 or NUP107) disperses the outer ring and cytoplasmic fibrils without disassembly of inner ring members. Conversely, rapid degradation of the inner ring complex component NUP188 disrupts the inner ring without dislodging outer ring members. We also found that depletion of NUP93 destabilized all NPC domains, indicating that it has a unique role as a lynchpin of NPC structure. Our data highlight the modular nature of NPC organization, suggesting that the outer and inner ring complexes do not extensively rely on each other for structural stability after NPC assembly is complete. This dynamic assessment provides new insights regarding the remarkable structural independence of domains within the NPC.

cell biology↗

bioRxiv2020

G4C2 repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD

Nucleocytoplasmic transport, controlled by the nuclear pore complex, has recently emerged as a pathomechanism underlying neurodegenerative diseases including C9orf72 ALS/FTD. However, little is known about the underlying molecular events and the underlying biology in human neurons. Using super resolution structured illumination microscopy of twenty three nucleoporins in nuclei from C9orf72 iPSC derived neurons and postmortem human tissue we identify a unique subset of eight nucleoporins lost from human neuronal nuclei. POM121, an integral transmembrane nucleoporin, appears to coordinate the composition of the nucleoporins within human neuronal nuclei ultimately impacting nucleocytoplasmic transport, and subsequent cellular toxicity in C9orf72 iPSNs. These data suggest that POM121 is a critical nucleoporin in the maintenance of the nuclear localization of specific nucleoporins in human neurons. Moreover, loss of nuclear POM121, as a result of expanded C9orf72 ALS/FTD repeat RNA, initiates a pathological cascade affecting nucleoporin composition within neuronal nuclei, nuclear pore complex function, and overall downstream neuronal survival.

neuroscience↗

bioRxiv2017

Representational dynamics of task context and its influence on visual object processing

Despite the importance of an observers goals in determining how a visual object is categorized, surprisingly little is known about how humans process the task context in which objects occur and how it may interact with the processing of objects. Using magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI) and multivariate techniques, we studied the spatial and temporal dynamics of task and object processing. Our results reveal a sequence of separate but overlapping task-related processes spread across frontoparietal and occipitotemporal cortex. Task exhibited late effects on object processing by selectively enhancing task-relevant object features, with limited impact on the overall pattern of object representations. Combining MEG and fMRI data, we reveal a parallel rise in task-related signals throughout the cerebral cortex, with an increasing dominance of task over object representations from early to higher visual areas. Collectively, our results reveal the complex dynamics underlying task and object representations throughout human cortex.

neuroscience↗